2010年6月17日，美国食品药品管理局(FDA)和赛诺菲-安万特公司宣布化疗药Jevtana (cabazitaxel)获准与强的松联合用于前列腺癌的治疗。详言之，Jevtana适用于多烯紫杉醇（晚期前列腺癌常用药）治疗期间或之后病情已发生恶化的转移性激素难治性前列腺癌(mHRPC)患者。

Jevtana接受了FDA优先审核程序的评估，药物快速审批通道将审批时间缩短为6个月，这可能会大大推进治疗，或为无适当治疗药的疾病提供一种疗法。

一项涉及755例患者的单独的III期研究证实了Jevtana的安全性和有效性。所有受试者之前均接受过多烯紫杉醇治疗。该研究旨在测定接受Jevtana联合强的松的男性相对于接受米托蒽醌联合强的松治疗者的总体生存期。接受Jevtana治疗方案的患者中位总体生存期为15.1个月，而接受米托蒽醌治疗方案者为12.7个月。研究结果证实，与接受有效化疗方案(由标准剂量的米托蒽醌与强的松构成)的患者相比，服用Jevtana配伍强的松的患者死于mHRPC的风险减少30%，具有统计学意义 [危险比，0.70(95%可信区间：0.59~0.83)；P < 0.0001] 。研究者采用实体瘤疗效评价(RECIST)标准，对cabazitaxel治疗组与米托蒽醌治疗组评估的肿瘤有效率分别为14.4% 和 4.4% (P =0.0005)。该试验的两个亚组均未观察到完全有效。

Jevtana治疗组患者报告的不良反应包括中性粒细胞减少、贫血、白细胞减少、血小板减少、腹泻、疲乏、恶心、呕吐、便秘、无力以及肾衰。

在末次试验给药后的30天内，在除病情进展以外其他原因所致的死亡方面，Jevtana治疗组中报告了18例(5%)，而米托蒽醌治疗组中报告了3例(<1%)。Jevtana治疗组中最常见的致死性不良反应为感染(5例)和肾衰(4例)。Jevtana预计于2010年夏季在美国上市。

JEVTANA
Manufacturer:
Sanofi-aventis
Pharmacological Class:
Antineoplastic (taxane &shy;antimicrotubule agent).
Active Ingredient(s):
Cabazitaxel 60mg/1.5mL; soln for IV infusion after dilution; contains polysorbate 80, diluent contains ethanol.
      
Indication(s):
In combination with prednisone, &shy;hormone-refractory metastatic prostate cancer &shy;previously treated with a docetaxel-containing regimen.
Pharmacology:
Cabazitaxel is a semisynthetic taxane antineoplastic agent prepared from an &shy;extract of yew needles. Cabazitaxel is a &shy;microtubule inhibitor that binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions. It has been shown to have activity in tumor models that were insensitive to docetaxel chemotherapy as well as in those that were docetaxel-sensitive.
Cabazitaxel is extensively metabolized by the &shy;liver, and it is not recommended for use in patients with impaired hepatic function due to a probable increase in cabazitaxel levels and toxicity.

Clinical Trials:
Cabazitaxel was compared to mitoxantrone in a multicenter, randomized, open-label study in 755 patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.
Patients were randomized to receive either cabazitaxel (25mg/m2 every 3 weeks for up to 10 cycles with prednisone 10mg daily) or mitoxantrone (12mg/m2 every 3 weeks for up to 10 cycles with prednisone 10mg daily).
Patients with hepatic impairment, hypertension, and certain cardiac conditions were excluded from the trial.
In an intent-to-treat analysis, the median survival time for the cabazitaxel group was 15.1 months, compared to 12.7 months for mitoxantrone; 61.9% of the patients in the cabazitaxel group died by the 30th month, compared to 74% in the mitoxantrone arm.
The investigator-assessed tumor response was higher in the cabazitaxel group (14.4%) compared to the mitoxantrone group (4.4%).

Legal Classification:
Rx
Adults:
Pretreat with IV antihistamine, cortico&shy;steroid, and H2 blocker 30 min before each dose (see literature) and with antiemetic (IV or oral as needed). 25mg/m2 by IV infusion over 1 hour &shy;every 3 weeks, with oral prednisone 10mg/day during treatment. Do not treat if neutrophil count ≤1,500 cells/mm3. Prolonged grade ≥3 neutropenia (>1 week), febrile neutropenia, grade ≥3 diarrhea: delay treatment and/or reduce dose to 20mg/m2 (see literature). Discontinue if reactions persist &shy;after dosing at 20mg/m2.
Children:
Not recommended.
Contraindication(s):
Baseline neutrophil count ≤1,500cells/mm3. Allergy to polysorbate 80.

Warnings/Precautions:
Do CBC weekly in 1st cycle and &shy;before each subsequent cycle. Increased risk of neutropenia complications; consider G-CSF prophylaxis. Hepatic impairment: not recommended. Severe renal impairment (CrCl <30mL/min) or ESRD. Elderly (increased susceptibility to adverse reactions); monitor closely. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended.
Interaction(s):
Avoid strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, saquinavir,voriconazole) (may potentiate cabazitaxel); caution with moderate CYP3A4 inhibitors.
Avoid strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, phenobarbital) (may antagonize cabazitaxel). Avoid St. John’s Wort.
Adverse Reaction(s):Bone marrow suppression(esp.neutropenia,anemia,leukopenia, thrombo&shy;cytopenia), febrileneutropenia, GI upset (esp. &shy;diarrhea, may be fatal), renalfailure,fatigue,&shy;constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia,cough,arthralgia,&shy;alopecia, hypersensitivity reactions (eg, rash, hypotension, bronchospasm).
How Supplied:
Kit (single-use vial + diluent)—1

Last Updated:
9/2/2010